Irreversible Electroporation (NanoKnife ®) and Immunotherapy for the Treatment of Stage IV Colorectal Cancer

NCT06047015 | Not Yet Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: IREIMMU
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this pilot clinical trial is to learn about the combination of immune boosting drugs and irreversible electroporation (IRE) in patients with colon cancer that has spread to the liver (metastasis). The main questions it aims to answer are:

1. 1.to document the rate of complications associated with combining IRE with immune boosting drugs.
2. 2.After one liver metastasis is treated with IRE and immune boosting drugs, what is the change in the size of the non-IRE-treated liver metastases?
3. 3.What is the immune response (measured in a blood sample) when IRE is combined with one or two types of immune boosting drugs?

Conditions

Liver Metastasis Colon Cancer

Outcome Measures

Primary Outcomes (3)

• Complications

  Complications (Clavien-Dindo classification of complications) at 30 days. The Clavien-Dindo Classification of Complications involves assigning a numbered classification to each complication, from 1-5, with 1 being a complication without need for any intervention required to 5 which is death of the patient. (a higher number indicates a higher severity). This is a validated measure in use for over 25 years.

  30 days

• Complications

  Complications (Clavien-Dindo classification of complications) at 90 days. The Clavien-Dindo Classification of Complications involves assigning a numbered classification to each complication, from 1-5, with 1 being a complication without need for any intervention required to 5 which is death of the patient. (a higher number indicates a higher severity). This is a validated measure in use for over 25 years.

  90 days

• Abscopal effect: percent change in non-treated colorectal liver metastasis.

  Two radiologists (one diagnostic and the other interventional) will examine the scans of all patients. They will select a colorectal metastasis from the scan just before the intervention that is between 2-3.2 cm in maximal diameter, accessible to percutaneous ablation, and treatable according to the interventional radiologist's opinion. Another metastasis, with a maximal diameter of less than 4 cm, will be selected to monitor for the abscopal effect (reduction in size of a colorectal liver metastasis that was not treated with IRE). After 3 months, the radiologists will review the imaging again. They will assess the treatment mass area for any contrast uptake indicating incomplete ablation. The second metastasis will be measured in the same dimensions as before treatment. The difference in maximal diameter of the second metastasis will be calculated as (diameter before IRE - diameter after IRE) / diameter before IRE and expressed as a percentage.

  3 months from the time of IRE

Secondary Outcomes (11)

• Tumor-specific immune response: distribution on flow-cytometry plot

  Day 8

• Tumor-specific immune response: serum cytokine concentrations

  Day 8

• Tumor-specific immune response: distribution on flow-cytometry plot.

  Day 14

• Tumor-specific immune response: serum cytokin concentrations

  Day 14

• Tumor-specific immune response: distribution on flow-cytometry plot.

  Day 30

Study Arms (2)

IRE plus Checkpoint Inhibitor

EXPERIMENTAL

Nivolumab: Patients will receive 240 mg nivolumab (dissolved in 250 mL NaCl 0.9%) administered intravenously over 30 minutes. The first dose will take place one or two days before the IRE treatment. The second and third doses will be given 2 and 4 weeks post-IRE. Bloodwork will be done just prior to each treatment. IRE is performed in the CT scanner. Patients will receive a general anesthetic, and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al.

Combination Product: IRE plus checkpoint inhibitor

IRE plus Checkpoint Inhibitor plus CpG Oligodeoxynucleotides (CpG-ODN)

EXPERIMENTAL

Patients will receive 240 mg nivolumab as above and also receive 8 mg of CpG-ODN dissolved in 1 mL normal saline administered peritumorally just before the IRE treatment. Three or four electrodes will be placed using a combination of ultrasound and CT guidance in preparation for treatment. Then using the electrodes as landmarks, injection of ¼ or 1/3 cc of the CpG-ODN solution will be performed near each of the 3 or 4 electrodes to achieve a peritumoral administration of the drug. IRE is performed in the CT scanner. Patients will receive a general anesthetic and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al.

Combination Product: IRE plus Checkpoint Inhibitor plus CpG-ODN

Interventions

IRE plus checkpoint inhibitor COMBINATION_PRODUCT

Nivolumab: Patients will receive 240 mg nivolumab (dissolved in 250 mL NaCl 0.9%) administered intravenously over 30 minutes. The first dose will take place one or two days before the IRE treatment. The second and third doses will be given 2 and 4 weeks post-IRE. Bloodwork will be done just prior to each treatment.

IRE plus Checkpoint Inhibitor

IRE plus Checkpoint Inhibitor plus CpG-ODN COMBINATION_PRODUCT

Patients will receive 240 mg nivolumab as above and also receive 8 mg of CpG-ODN dissolved in 1 mL normal saline administered peritumorally just before the IRE treatment. Three or four electrodes will be placed using a combination of ultrasound and CT guidance in preparation for treatment. Then using the electrodes as landmarks, injection of ¼ or 1/3 cc of the CpG solution will be performed near each of the 3 or 4 electrodes to achieve a peritumoral administration of the drug. IRE is performed in the CT scanner. Patients will receive a general anesthetic and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al.

IRE plus Checkpoint Inhibitor plus CpG Oligodeoxynucleotides (CpG-ODN)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-proven colorectal liver metastases with at least one measuring \< 3.5 cm in diameter and accessible to percutaneous IRE such that a complete ablation of the lesion is possible.
• Prior resection of the colorectal cancer primary.
• The imaging has been reviewed in multi-disciplinary Rounds and the colorectal liver metastases have been deemed unresectable.
• Patient has undergone chemotherapy and has not converted to resectable disease.
• Radiologic evidence of stable disease for at least two months on systemic therapy for colorectal cancer (may have had prior partial response or disease progression)
• Microsattelite instability (MSI)-stable or mismatch-proficient tumors
• Patient has HLA phenotype of Human Leukocyte Antigen (HLA) A1 or HLA A2.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Size of the metastasis being treated with IRE \> 3.2 cm or \< 2 cm.
• Size of any non-IRE-treated liver metastasis \> 4 cm
• Pregnancy
• Major comorbid disease
• Active autoimmune disease
• Bone or brain or peritoneal metastases.
• MSI High disease
• Patients with cardiac arrhythmia other than rate controlled atrial fibrillation.
• Metal implant that cannot be removed within 10 cm of the area to be treated.
• Peritoneal disease.
• Poor performance status
• Cirrhosis

Sponsors & Collaborators

• University of Saskatchewan: lead

MeSH Terms

Interventions

Electroporation; CPG-oligonucleotide

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Central Study Contacts

Mike AJ Moser, MD, MSc

CONTACT

306-655-5319; mike.moser@usask.ca

Shahid Ahmed, MD

CONTACT

306-655-2630; shahid.ahmed@saskcancer.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery

Model Details: This will be a pilot study examining 6 patients treated with IRE and checkpoint inhibitor (first 6, non-randomized) and 6 patients treated with IRE and checkpoint inhibitor and CpG

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: September 21, 2023
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share